ESA-SRB-AOTA 2019

Positive Thyroid Receptor Blocking Antibodies identified in patients with severe hypothyroidism- Case report. (#636)

Julie Sherfan 1 , Joel Lasschuit 2 3 , Nimalie Perera 1 4 5 , David Sullivan 1 2
  1. Department of Chemical Pathology, NSW Health Pathology, Royal Prince Alfred, Camperdown, NSW, Australia
  2. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  3. Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia
  4. Department of Chemical Pathology, Sydney Children's Hospital Westmead, Westmead, NSW, Australia
  5. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Introduction:

Graves’ disease is traditionally thought to be caused by ‘stimulatory’ thyroid receptor autoantibodies (TRAB), resulting in hyperthyroidism. However, TRAB differ in function (stimulating-TSI, blocking-TBI or neutral), and result in variable thyroid dysfunction and orbitopathy1.

We present a patient with hypothyroidism and elevated TRAB, and another patient with initial hyperthyroidism and elevated TRAB requiring treatment, who then developed progressive hypothyroidism despite therapy cessation.

Case 1:

A 76-year-old female was referred for advice, due to difficulty stabilising thyroxine replacement for primary hypothyroidism. Comorbidities included treated diffuse large B-cell lymphoma, rheumatoid arthritis in remission, and dilated cardiomyopathy.

She initially presented with heart failure, hyponatraemia and hypercholesterolemia, with TSH 67.4mIU/L, fT4 6.3pmol/L, fT3 1.4pmol/L, anti-TPO antibody <5 IU/mL, thyroglobulin antibody 699IU/mL, and TRAB  14IU/L. Thyroid was small volume on ultrasound.

Of note, TRAB remained elevated since diagnosis (even after cessation of biotin supplements). Possibility of TBI was investigated.

Case 2:

A 39-year-old female presented with signs and symptoms of severe hyperthyroidism. TSH was <0.01mU/L, fT4 >100pmol/L, fT3 >50pmol/L, thyroglobulin 11.9ug/L, thyroglobulin antibody 864IU/mL and TRAB 41IU/L. She was treated with Carbimazole (8-weeks), but treatment was stopped due to hypothyroidism with TSH 57.5 mU/L, fT4 6.7 pmol/L and fT3 4.0 pmol/L, that progressed despite stopping therapy. Possibility of TBI was investigated.

Methods:

Both serums were tested on the Thyretain® TSI/ TBI bioassays (Quidel, San Diego, USA).

Results:

Serum of both cases negative for TSI, but TBI in case 1 was 95% (RI<34% Inhibition) and TBI in case 2 was 54% (RI<34% Inhibition).

Conclusion:

These cases illustrate the clinical utility of the of the Thyretain® TSI / TBI bioassay to distinguish   subclasses of TRAB by ‘functional’ measurement of cAMP produced in transfected cell culture. This creates a two-dimensional picture and will be useful in managing and monitoring patients with complex thyroid dysfunction.  

  1. "Data on Ophthalmic Plastic and Reconstructive Surgery Detailed by Researchers at Department of Endocrinology (Predicting the Development of Orbitopathy in Graves Thyroidopathy Patients: The Potential Role of TSI Testing)." Health & Medicine Week, 23 Oct. 2015, p. 1556
  2. Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features, (J Clin Endocrinol Metab 103: 3010–3018, 2018)